RELATED ART
Published German patent application P 32 29 540.5 discloses resorbable waxes for the mechanical staunching of blood on hard body tissue, and particularly on bones. The waxes are characterized in that they comprise wax-like polyester oligomers of lower hydroxycarboxylic acids which range from viscous fluids to solids at body temperature. By virtue of their structure, these waxes are degradable by the body's metabolic processes, the degradation rate being adjustable in a known manner. Oligomers of glycolic acid are degraded more quickly by metabolic processes than oligomers of lactic acid. Accordingly, the degradation rate can be regulated, for example, by mixed esterification of the two hydroxycarboxylic acids. The preferred waxes have average molecular weights in the range from about 200 to 1,500 and more preferably in the range from about 300 to 1,000.
According to the published German patent application cited above, monofunctional and/or difunctional alcohols or carboxylic acids or carboxylic anhydrides and/or primary or secondary monoamines may be used to regulate the average molecular weight of the polyester oligomers. A definitive average molecular weight may be determined in advance in known manner by selecting suitable ratios of hydroxycarboxylic acid and the monofunctional or difunctional component. It is known that the reaction products obtained are not uniform in their degree of oligomerization, and contain certain quantities of the starting components.
German patent application P 37 16 302.7 discloses a further optimization of resorbable waxes for the mechanical staunching of blood on hard body tissue. According to this patent application, body-compatible and, in particular, tissue-compatible waxes are obtained when, in accordance with the disclosure of the published German patent application cited above, a certain trifunctional alcohol, namely glycerol, is used to adjust the average molecular weight. The combination of glycerol with oligoesters of lactic acid and/or glycolic acid leads to degradable wax-like components which, on implantation in living body tissue, are distinguished by particularly pronounced compatibility with the body.
Applicants' earlier patent application then discloses that unwanted tissue damage can be avoided particularly safely when through the production process and through subsequent purification of the degradable wax, its content of unreacted carboxyl groups is greatly reduced or is almost completely eliminated. Free carboxyl groups are present in the reaction mixture in the absence of the molecular-weight-regulating dicarboxylic acids proposed in Applicants' above-cited published German patent application. The statistical molecular weight distribution which occurs directly from the production of the waxes always leaves a certain number of free carboxyl groups, which are present at least predominantly as free monomeric hydroxycarboxylic acids, in the oligomeric reaction mixture, even when the desired average number value is adjusted for the molecular weight.
In one particularly preferred embodiment of the invention described in the earlier application, the wax-like material is at least largely freed from its content of unreacted starting components. In particular, the content of unreacted hydroxycarboxylic acids is reduced to residual contents below 0.5% by weight and preferably to residual contents below about 0.2% by weight. In general, the residual contents of unreacted hydroxycarboxylic acids in the waxes will be at or below 0.1% by weight.
The unreacted reactants are said to be preferably removed by a precipitation process in which the desired oligomer fractions are precipitated from a solution or suspension while the unreacted components and/or reaction products of low molecular weight remain in solution.
The problem addressed by the present invention is to further improve resorbable bone waxes in several respects with particular emphasis on the following considerations:
The present invention also seeks to increase the tissue compatibility of the wax implanted in the human or animal body by reducing or substantially eliminating the content of free carboxyl groups in the reaction product. In addition the invention improves the practical handling properties of the waxes to make the work of the surgeon easier. Oligoesters of lactic acid are frequently distinguished by such pronounced viscosity that the wax can be difficult to handle during an operation. The stringing of the oligoester rich in lactic acid, which is particularly useful on physiological grounds, prevents rapid and interference-free handling during the removal of material from the package and during sealing of the bone. Such difficulties arise to only a limited extent, if at all, in the case of oligomeric esters of glycolic acid. For physiological reasons, however, it may be desirable to use waxes based largely on lactic acid. It is known that the degradation of glycolic acid by the body's metabolism takes place by way of oxalic acid. Degradation of lactic acid in the body does not form oxalic acid. If the prevention or restriction of additional oxalic acid formation in the body is indicated, waxes based predominantly on lactic acid will become particularly important for use in operations where a bone wax is used. Accordingly, it is important that the bone wax is easy to handle in practice.